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Yorodumi- EMDB-4358: Coupling specificity of heterotrimeric Go to the serotonin 5-HT1B... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4358 | |||||||||
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Title | Coupling specificity of heterotrimeric Go to the serotonin 5-HT1B receptor | |||||||||
Map data | Map after RELION "postprocessing" sharpened with a B=-200 and weighted by FSC. | |||||||||
Sample |
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Function / homology | Function and homology information guanyl nucleotide binding / voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels / negative regulation of gamma-aminobutyric acid secretion / serotonergic synapse / G protein-coupled serotonin receptor complex / adenylate cyclase-inhibiting serotonin receptor signaling pathway / regulation of behavior / negative regulation of synaptic transmission, GABAergic / response to mineralocorticoid / Serotonin receptors ...guanyl nucleotide binding / voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels / negative regulation of gamma-aminobutyric acid secretion / serotonergic synapse / G protein-coupled serotonin receptor complex / adenylate cyclase-inhibiting serotonin receptor signaling pathway / regulation of behavior / negative regulation of synaptic transmission, GABAergic / response to mineralocorticoid / Serotonin receptors / negative regulation of serotonin secretion / drinking behavior / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / cellular response to temperature stimulus / bone remodeling / serotonin binding / negative regulation of synaptic transmission, glutamatergic / vasoconstriction / G protein-coupled serotonin receptor activity / : / G protein-coupled receptor internalization / vesicle docking involved in exocytosis / neurotransmitter receptor activity / regulation of synaptic vesicle exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / regulation of dopamine secretion / cellular response to alkaloid / calyx of Held / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / muscle contraction / positive regulation of vascular associated smooth muscle cell proliferation / presynaptic modulation of chemical synaptic transmission / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to cocaine / locomotory behavior / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / cellular response to xenobiotic stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / chemical synaptic transmission / response to ethanol / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.78 Å | |||||||||
Authors | Garcia-Nafria J / Nehme R / Edwards P / Tate CG | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Nature / Year: 2018 Title: Cryo-EM structure of the serotonin 5-HT receptor coupled to heterotrimeric G. Authors: Javier García-Nafría / Rony Nehmé / Patricia C Edwards / Christopher G Tate / Abstract: G-protein-coupled receptors (GPCRs) form the largest family of receptors encoded by the human genome (around 800 genes). They transduce signals by coupling to a small number of heterotrimeric G ...G-protein-coupled receptors (GPCRs) form the largest family of receptors encoded by the human genome (around 800 genes). They transduce signals by coupling to a small number of heterotrimeric G proteins (16 genes encoding different α-subunits). Each human cell contains several GPCRs and G proteins. The structural determinants of coupling of G to four different GPCRs have been elucidated, but the molecular details of how the other G-protein classes couple to GPCRs are unknown. Here we present the cryo-electron microscopy structure of the serotonin 5-HT receptor (5-HTR) bound to the agonist donitriptan and coupled to an engineered G heterotrimer. In this complex, 5-HTR is in an active state; the intracellular domain of the receptor is in a similar conformation to that observed for the β-adrenoceptor (βAR) or the adenosine A receptor (AR) in complex with G. In contrast to the complexes with G, the gap between the receptor and the Gβ-subunit in the G-5-HTR complex precludes molecular contacts, and the interface between the Gα-subunit of G and the receptor is considerably smaller. These differences are likely to be caused by the differences in the interactions with the C terminus of the G α-subunit. The molecular variations between the interfaces of G and G in complex with GPCRs may contribute substantially to both the specificity of coupling and the kinetics of signalling. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4358.map.gz | 5.3 MB | EMDB map data format | |
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Header (meta data) | emd-4358-v30.xml emd-4358.xml | 20 KB 20 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4358_fsc.xml | 6.3 KB | Display | FSC data file |
Images | emd_4358.png | 125.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4358 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4358 | HTTPS FTP |
-Validation report
Summary document | emd_4358_validation.pdf.gz | 273.4 KB | Display | EMDB validaton report |
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Full document | emd_4358_full_validation.pdf.gz | 272.5 KB | Display | |
Data in XML | emd_4358_validation.xml.gz | 8.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4358 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4358 | HTTPS FTP |
-Related structure data
Related structure data | 6g79MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10308 (Title: Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go Data size: 8.0 TB / Data #1: Unaligned movies [micrographs - multiframe] Data #2: Extracted particles [picked particles - multiframe - processed]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4358.map.gz / Format: CCP4 / Size: 12.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Map after RELION "postprocessing" sharpened with a B=-200 and weighted by FSC. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : Serotonin 5-HT1B receptor bound to a mini-Go heterotrimer
+Supramolecule #1: Serotonin 5-HT1B receptor bound to a mini-Go heterotrimer
+Supramolecule #2: 5-HT1B receptor
+Supramolecule #3: Beta subunit
+Supramolecule #4: mini-Go
+Supramolecule #5: Gamma subunit
+Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #3: Guanine nucleotide-binding protein G(o) subunit alpha
+Macromolecule #4: 5-hydroxytryptamine receptor 1B
+Macromolecule #5: 2-[5-[2-[4-(4-cyanophenyl)piperazin-1-yl]-2-oxidanylidene-ethoxy]...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2.2 mg/mL | ||||||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number real images: 5737 / Average exposure time: 60.0 sec. / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |